Juana Marin

Initial use of a novel noninvasive vagus nerve stimulator for cluster headache treatment.

Objective: To report our initial experience with a novel device, designed to provide portable, noninvasive, transcutaneous stimulation of the vagus nerve, both acutely and preventively, as a treatment for cluster headache. Methods: Patients with cluster headache (11 chronic, 8 episodic), from 2 centers, including 7 who were refractory to drug treatment, had sufficient data available for analysis in this open-label observational cohort study. The device, known as the gammaCore, was used acutely to treat individual attacks as well as to provide prevention. Patient-estimated efficacy data were collected by systematic inquiry during follow-up appointments up to a period of 52 weeks of continuous use. Results: Fifteen patients reported an overall improvement in their condition, with 4 reporting no change, providing a mean overall estimated improvement of 48%. Of all attacks treated, 47% were aborted within an average of 11 ± 1 minutes of commencing stimulation. Ten patients reduced their acute use of high-flow oxygen by 55% with 9 reducing triptan use by 48%. Prophylactic use of the device resulted in a substantial reduction in estimated mean attack frequency from 4.5/24 hours to 2.6/24 hours (p < 0.0005) posttreatment. Conclusion: These data suggest that noninvasive vagus nerve stimulation may be practical and effective as an acute and preventive treatment in chronic cluster headache. Further evaluation of this treatment using randomized sham-controlled trials is thus warranted. Classification of evidence: This study provides Class IV evidence that for patients with cluster headache, transcutaneous stimulation of the vagus nerve aborts acute attacks and reduces the frequency of attacks.

Glutamatergic fine tuning with ADX-10059: a novel therapeutic approach for migraine?

Importance of the field: Migraine is an episodic, substantially inherited brain disorder affecting 15% of adults in Western Europe and North America, and is one of the commonest reasons for patients to see their physicians. While the World Health Organization considers that severe migraine can be as disabling as quadriplegia, unfortunately the condition remains undertreated. Until the 1990s, specific migraine therapies were limited to ergot derivatives. Areas covered in this review: The triptans, serotonin 5-HT1B/1D receptor agonists, revolutionized the acute management of migraine patients. However, although the triptans are generally effective and safe, not all patients can take them and many do not respond especially to oral therapies. Recently, progress has been made on the therapeutic front, particularly with new acute treatments. This review will focus on the therapeutic potential of ADX10059, a metabotropic glutamate receptor 5, negative allosteric modulator (mGluR5 NAM), in migraine. Data from a proof-of-concept study in episodic migraineurs demonstrated a significant improvement following acute treatment. A large European multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study is currently investigating the efficacy, safety and tolerability of the compound for migraine prevention. What the reader will gain: The reader will have the basic principles of migraine management and the potential for glutamate-targeted approaches. Take home message: Targeting glutamatergic transmission in migraine may provide a novel preventive therapy that is effective and well-tolerated.

Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A randomized, double-blind, sham-controlled ACT2 study

Background Clinical observations and results from recent studies support the use of non-invasive vagus nerve stimulation (nVNS) for treating cluster headache (CH) attacks. This study compared nVNS with a sham device for acute treatment in patients with episodic or chronic CH (eCH, cCH). Methods After completing a 1-week run-in period, subjects were randomly assigned (1:1) to receive nVNS or sham therapy during a 2-week double-blind period. The primary efficacy endpoint was the proportion of all treated attacks that achieved pain-free status within 15 minutes after treatment initiation, without rescue treatment. Results The Full Analysis Set comprised 48 nVNS-treated (14 eCH, 34 cCH) and 44 sham-treated (13 eCH, 31 cCH) subjects. For the primary endpoint, nVNS (14%) and sham (12%) treatments were not significantly different for the total cohort. In the eCH subgroup, nVNS (48%) was superior to sham (6%; p < 0.01). No significant differences between nVNS (5%) and sham (13%) were seen in the cCH subgroup. Conclusions Combing both eCH and cCH patients, nVNS was no different to sham. For the treatment of CH attacks, nVNS was superior to sham therapy in eCH but not in cCH. These results confirm and extend previous findings regarding the efficacy, safety, and tolerability of nVNS for the acute treatment of eCH.

Nociception-specific blink reflex: a double-blinded placebo-controlled pharmacological study in 21 healthy males

Ultrahigh molecular weight polyethylene (UHMWPE) is used in orthopaedic implants due to outstanding wear properties. In spite of the low wear behaviour of UHMWPE compared to other polymers, wear remains a major problem in total joint replacements. Submicron wear particles cause foreign body response leading to bone resorption (osteolysis) and loosening of implant components. This further limits the life expectancy of hip prostheses [1-2]. Therefore, improving the wear resistance of UHMWPE can substantially extend the clinical life span of total hip prostheses. It was recently reported that quasicrystalline fillers may significantly improve wear resistance in polymer-based composites [3-4].

Noninvasive Vagus Nerve Stimulation for Treatment of Indomethacin-Sensitive Headaches

Noninvasive Vagus Nerve Stimulation for Treatment of Indomethacin-Sensitive Headaches Trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders that are characterized by attacks of unilateral pain of varying duration and prominent, ipsilateral cranial autonomic symptoms, such as lacrimation, conjunctival injection, nasal congestion, rhinorrhea, or periorbital edema. The TACs include cluster headaches, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing or cranial autonomic symptoms.1 Paroxysmal hemicrania (PH) attacks last 2 to 30 minutes and typically occur several times per day.1,2 Hemicrania continua (HC) is characterized by continuous pain with exacerbations lasting for hours or days.3 Both are defined by their response to indomethacin; a high dose of 225 mg daily or greater may be needed1 and lifelong treatment is frequently required. Unfortunately, indomethacin is often poorly tolerated because of adverse effects, such as nausea, abdominal pain, or gastric bleeding. Transcutaneous stimulation of the vagus nerve with the GammaCore (electroCore, LLC) has been effective for the acute treatment of episodic cluster headaches in 2 randomized shamcontrolled trials,4,5 raising the possibility that this treatment might be effective for other TACs including HC.6 We began treating patients with PH or HC who were unable to tolerate

Proof of concept: short-term non-invasive cervical vagus nerve stimulation in patients with drug-refractory gastroparesis

Background Gastric electric stimulation (GES) is a treatment approach to refractory gastroparesis, possibly acting centrally via afferent vagus nerve stimulation (VNS). Non-invasive VNS (nVNS) is a potential alternative to GES that could eliminate the safety risks of or identify likely responders to implantable neurostimulators. Objective This open-label proof-of-concept study assessed the effects of nVNS in patients with severe drug-refractory gastroparesis. Methods Patients used the Gastroparesis Cardinal Symptom Index (GCSI) to grade symptoms in diaries daily for 2 weeks before treatment (baseline) and during ≥3 weeks of nVNS therapy. Adverse events (AEs) were also diarised. Treatment was self-administered using an nVNS device (gammaCore, electroCore) and consisted of 120 s stimulations to the vagus nerve in the neck (two stimulations to each side three times daily during weeks 1 and 2; three stimulations to each side three times daily during week 3 and beyond). Response was defined as a ≥1 point decrease from baseline in GCSI score. Results Thirty-five patients enrolled; 23 were compliant with study procedures and were included in the analysis; 7 continued treatment beyond 3 weeks. Response rates were 35% (8/23) at 3 weeks and 43% (10/23) for the duration of therapy (3–6 weeks). For the entire cohort and the 10 responders, improvements from baseline were noted for mean total GCSI and GCSI subscale scores (nausea/vomiting, postprandial fullness/early satiety, bloating). No serious AEs were reported. Conclusions These preliminary results provide a signal that nVNS may be useful for treating refractory gastroparesis. Larger controlled studies are warranted.

Flunarizine in migraine-related headache prevention: results from 200 patients treated in the UK

For over 20 years, as a group we have been using flunarizine in primary headache disorders. Flunarizine is widely used in Europe, but not licensed in the UK. In September 2014, the National Institute for Clinical Excellence published supportive guidelines for flunarizine use in migraine, based on randomized controlled evidence that it is as effective as propranolol and topiramate in adults.

MIGRAINE IN KLEINE-LEVIN SYNDROME

Background Kleine-Levin syndrome (KLS) is a rare sleep disorder characterised by recurrent episodes of hypersomnia, cognitive impairment and behavioural changes. The aetiology is unclear, but current opinion focuses on dysfunction within diencephalic pathways. In our experience patients and their relatives often describe severe headache, photophobia and phonophobia during episodes. However headache and other migrainous symptoms are infrequently described in case reports and are not mentioned in the ICSD-2 classification. Aims and objectives: Migraine as a risk marker, a symptomatic feature or an aetiological factor may have been overlooked in the characterisation of KLS. The aim of this study was to investigate the frequency and features of migraine in eleven KLS patients. Methods A proforma was created to identify typical migrainous symptoms and associations. Interviews were conducted by telephone. Collateral histories were obtained to complete clinical pictures, which can be distorted by amnesia. Results Seven patients (64%) experienced migraine between KLS episodes. Atypical and migrainous features of KLS identified during episodes included: headache (73%), photophobia (55%), phonophobia (55%) and nausea (27%). Mean KLS episode duration was 30.4 days in the migraine group vs 12.8 days in the non-migraineurs. Conclusions The association with migraine deserves further investigation, not only as a reliable risk marker but for exploration of the pathophysiology of KLS and novel therapeutic avenues. Initial use of triptans in two of our patients has yielded encouraging results. We encourage others to look for signs of migraine in their patients and consider the use of appropriate therapy.